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Status |
Public on Jun 21, 2012 |
Title |
Role of miR-125b in B-cell acute lymphoblastic leukemia (B-ALL) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
B-cell acute lymphoblastic leukemia (B-ALL) is often associated with chromosomal translocations leading to the deregulation of proto-oncogenes. MicroRNAs can also be affected by chromosomal alterations and thus contribute to carcinogenesis. The microRNA miR-125b-1 is over-expressed in B-ALL cases with the t(11;14)(q24;q34) translocation, therefore we sought to determine the role of this microRNA in B-cell fate. We used murine pre-BI cells alongside murine and human leukemic B-cell lines to show that miR-125b expression enhances proliferation by targeting Bright/ARID3a, an activator of immunoglobulin heavy-chain transcription. Accordingly, this target gene was down-regulated in B-ALL patients with the t(11;14)(q24;q34) translocation. Repression of Bright/ARID3A blocked differentiation and conferred a survival advantage to Ba/F3 cells under IL3 starvation. In addition, over-expression of miR-125b protected pre-BI and leukemic B-cell lines from apoptosis through blockade of caspase activation via a mechanism that was independent of p53 and BAK1. In summary, miR-125b can act as an oncogene in B-ALL by targeting ARID3a and mediating its repression, thus leading to a blockage in differentiation, increased proliferation and inhibition of apoptosis.
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Overall design |
To identify specific targets of mir-125b, we overexpressed miR-125b as well as a control miRNA in 70Z/3 and 18-81 pre-B leukaemia cells. Chemically synthesized miRNA duplexes, called pre-miR-125b and miR-Neg, were purchased from Ambion. The cells were transfected with pre-miRNA at a final concentration of 10 nM using Lipofectamin RNAi MAX (Invitrogen) according to the manufacturer’s instructions. The medium was replaced 8 hours after transfection. RNA samples were harvested at 48 hours post-transfection. 2 independent experiments were carried out for a total of 8 samples labeled with Cy3 dye (one color design).
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Contributor(s) |
Puissegur M, Barbry P, Lebrigand K |
Citation(s) |
22469780 |
Submission date |
Jul 13, 2011 |
Last update date |
Jul 19, 2017 |
Contact name |
Kevin Lebrigand |
Organization name |
IPMC/CNRS
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Lab |
Functional Genomics Platform of Nice-Sophia-Antipolis, France.
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Street address |
660 route des lucioles
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City |
Valbonne - Sophia-Antipolis |
ZIP/Postal code |
06560 |
Country |
France |
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Platforms (1) |
GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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Samples (8)
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Relations |
BioProject |
PRJNA144619 |